Comparative approaches provide unique experimental models and a perspective of biological history of regulation of blood pressure. Therefore, knowledge obtained from studying lower animal forms should be very applicable towards the understanding of blood pressure control system in man. The aim of the proposed project is to test the hypothesis that the renin-angiotensin system (RAS) evolved phylogenetically as a humoral regulator in cardiovascular homeostasis. The hypothesis is based: a) on the morphological evidence that the juxtaglomerular cells emerged at an earlier stage of vertebrate phylogeny than the macula densa, b) on the physiological observations that angiotensin exerts a potent vasopressor action, and c) on the observation that hypotension and hemorrhage cause renin release in the aglomerular toadfish. On the other hand, there is no clear evidence that sodium depletion stimulates the RAS or that the RAS causes conservation of sodium in teleosts and amphibians. The primitive animals are ideal models to examine the function of a possible renal "vascular" receptor without the influence of the macula densa. We intend to approach the project from three directions: 1) To determine whether a renal "vascular" receptor for controlling renin release exists in bony fishes, or the adrenergic nervous system is also involved. These will be examined by changing renal perfusion pressure and measuring changes in renin secretion, and by studying the effects of adrenergic blocking drugs on renin release. 2) To define the chemical evolution of the angiotensin molecule, and study properties of angiotensin receptors in blood vessels in primitive animals. 3) To clarify the role of the RAS in the etiology of the elevated blood pressure in birds. Most of the birds examined show high blood pressure and frequent atherosclerosis, but little has been studied about humoral control of cardiovascular and renal function in relation to this elevated blood pressure. Recently we have adapted a radioimmunoassay method utilizing human angiotensin I antibody to measure renin activity in fishes and intend to apply it to other species.